AB0072 GLUCOCORTICOIDS MODIFY NOT ONLY THE PROPERTIES OF DENDRITIC CELLS, BUT ALSO PROGENITOR CELLS
Authors: Y. Kurochkina, A. Sizikov, E. Chernykh, T. Tyrinova
Journal: Annals of the Rheumatic Diseases (2022)

Background Dendritic cells (DCs) are universal antigen-presenting cells that can have both tolerant and immunosuppressive properties. Tolerogenic properties of DCs are mediated by activation T-regulatory cells, production of anti-inflammatory cytokines and activation T cell apoptosis. Currently, DC is an attractive object of study as a new treatment for rheumatoid arthritis. It is known that glucocorticoids make it possible to control properties of DCs to the tolerogenic side. Objectives The aim of the study is to investigate the effect of pulse therapy by glucocorticodes on the properties of DCs and peripheral blood monocytes from which DCs were generated. Methods Twenty five patients with rheumatoid arthritis were recruited in this study. All patients follow ACR/EULAR criteria (2010). All studies were performed after receiving informed consent. All patients received conventional synthetic DMARDs. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α, LPS as maturation stimuli was added on fourth day. The functions of DCs were evaluated by allostimulatory activity in mixed lymphocyte culture. The properties of DC were studied before pulse therapy (methylprednisolone 500mg №3) and 4 days after pulse therapy.The relative number of monocytes (classical CD14 ++ CD16 + , intermediate CD14 + CD16 + and nonclassical CD14 + CD16 ++ ) before and after pulse therapy was also studied in comparison with healthy donors. Results Prior to pulse therapy, the DCs from RA patients were characterized by a high ability to stimulate the proliferation of allogenic T-lymphocytes about 20000 cpm. After pulse therapy, the stimulating ability of DCs significantly decreased (9800 vs. 2000 cpm, p=0.04). Evaluation of the relative content of classical (CD14 ++ CD16 - ), intermediate (CD14 ++ CD16 + ) and nonclassical (CD14 + CD16 ++ ) monocytes of healthy donors (n=18) and RA patients (n=25) revealed a decrease in the relative content of CD14 ++ CD16 - cells in patients (Me 78 vs. 90%; p=0.02) and an increase in the proportion of CD14 ++ CD16 + (Me 4.0 vs. 2.0%; p=0.034) and CD14 + CD16 ++ monocytes (Me 5.0 vs. 1.5%; p=0.02). After the end of pulse therapy in RA patients, the relative content of CD14 ++ CD16 - cells increased (89 vs. 78%), and the proportion of CD14 + CD16 ++ monocytes decreased (1 vs. 5%), and RA patients no longer significantly differed in these indicators from healthy donors. Thus, a decrease in the content of CD14 + CD16 ++ cells in the monocytes population after pulse therapy was associated with a decrease in the effectiveness of DCs generated to stimulate the proliferation of allogenic T cells. Conclusion The effect of pulse therapy of glucocorticoids is associated not only with the ability of glucocorticoids to inhibit the maturation of IFN-DC and induce their tolerant phenotype at the stage of differentiation of monocytes into DCs, but also with the effect on the subpopulation of circulating monocytes that are precursors of DC. Disclosure of Interests None declared